The present inventors have formerly reported in Japanese Patent Application (OPI) No. 83791/80 (corresponding to U.S. Pat. No. 4,357,331) novel 7.beta.-(2D-2-amino-2-carboxyethylthioacetamido)-7.alpha.-methoxy-3-(1-met hyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid represented by the following formula (I): ##STR1## and its salt, such as the sodium salt of compound (I).
Compound (I) is prepared, for example, by the following reaction (A): ##STR2## or by the following reaction (B): ##STR3## The compound (I) is effective against various bacteria such as gram-positive bacteria, gram-negative bacteria (except Pseudomonas aeruginosa), and anaerobic bacteria, thus having a wide antibacterial spectrum. Especially, it exhibits a strong antibacterial activity against gram-negative bacteria and, in comparison with other cephalosporins, it exhibits excellent antibacterial activity against Bacteroides fragilis and Campylobacter jejuni. In addition, it exhibits a strong bactericidal effect on Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, etc. under short exposure. Further, it exhibits an antibacterial effect on bacteria in the stationary phase of growth.
The compound (I) possesses an excellent therapeutic effect on infectious diseases of mice induced by Klebsiella pneumoniae, Proteus morganii, Escherichia coli, Serratia marcescens, etc.
Acute toxicity testing of the compound (I) using mice revealed that LD.sub.50 of the compound when intravenously administered to female mice is 5,200 mg/kg and that of the compound when intravenously administered to male mice is 6,100 mg/kg. In subacute toxicity testing and chronic toxicity testing using rats and dogs, the compound (I) was found show low toxidity. In a teratogenecity test and special toxicity tests, too, toxicity of the compound was found to be within an acceptable range.
Clinical studies revealed that blood level of the compound (I) after intravenous application reaches the highest level immediately after the injection and stands at an effective level for a long time, thus the compound showing good pharmacodynamic properties. Half-value period of the compound in blood is about 2.5 hours, and recovery from urine is 90 to 95%. These results suggest that the compound (I) will exhibit the same excellent antibacterial activity when administered to humans as it has exhibited in vitro and in laboratory animals.
However, while the compound (I) has the above-described excellent antibacterial activity, it is somewhat colored in appearance, darkening with passage of time, and also its potency is unstable at elevated temperatures, thus rendering compound (I) unsuitable as a practical medicine.